Aging and hypertension cause similar changes in the wall structure of intracerebral arterioles. However, little data directly relate these structural changes with altered contractile function of the vessel wall or with dynamic changes in cerebrovascular resistance. Our overall objective is to study the biomechanical properties and responsiveness of isolated intracerebral arterioles from three strains of rat (F344, WKY and SHR) at 3, 12 and 16 to 24 months of age. These physiological characteristics will then be correlated with arteriolar wall structure from vessels fixed in vitro after physiologic study and in situ after pressure perfusion fixation.
The specific aims are: 1) to determine the effect of aging and hypertension on active stress development and wall compliance in cerebral arterioles; 2) to determine the relative effects of aging and hypertension on cerebrovascular reactivity and on sensitivity to putative metabolic and neurogenic modulators of cerebrovascular resistance; 3) to correlate biomechanical characteristics of intracerebral arterioles from aged and hypertensive rats and humans with morphological indicators of vessel wall mass: partial volumes of actin and connective tissue, cell volume and cell number. Structure-function relationships established for these well characterized animal models will be extended to human intracerebral arterioles obtained at operation. These studies should enhance our understanding of how the microcirculation is affected by aging and hypertension, and how these changes relate to the major pathophysiologic sequelae of hypertension in the brains of aged individuals, thrombotic infarction and intracerebral hemorrhage.
